Ashwagandha + DOXIL for Ovarian Cancer

Overseen By Whitney Goldsberry, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Sham Sunder Kakar

Must be taking: Liposomal doxorubicin

Must not be taking: Other anticancer drugs

Disqualifiers: Brain metastases, Active infection, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for people with recurrent ovarian cancer, where standard treatments like platinum-based chemotherapy have stopped working. The study explores how well Ashwagandha, a herbal supplement, can be used with DOXIL, a cancer drug, to improve patient outcomes. In the first phase, researchers will test different doses of Ashwagandha to find the most tolerable level. In the second phase, they will use the best dose to assess the combination's effectiveness in treating cancer. Women with recurrent ovarian cancer who have already tried platinum-based chemotherapy may be a good fit for this trial. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does require that you discontinue all prior cancer therapies at least 4 weeks before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have used DOXIL, a type of chemotherapy, in many patients with various cancers, including ovarian cancer. Safety data from these studies show that while DOXIL can cause side effects, it is generally considered safe. Common side effects include low blood cell counts and mouth sores, but proper care can manage these issues.

Research suggests that Ashwagandha might support the immune system and has potential as a cancer treatment. However, specific safety information about using Ashwagandha with DOXIL remains limited.

As this trial is in its early stages, some safety information is available, but researchers are still studying the full effects of the combination. The trial aims to find the best dose that people can handle without too many side effects. Participants will help researchers learn more about the safety of this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for ovarian cancer, which often include surgery, chemotherapy, and targeted therapy, the combination of DOXIL and Ashwagandha is unique because it integrates a traditional herbal supplement with a chemotherapy agent. Ashwagandha, known for its adaptogenic properties, is being tested for its potential to enhance the effectiveness of DOXIL while possibly reducing side effects. Researchers are excited because this combination could offer a new, holistic approach that not only targets the cancer cells but also supports the patient's overall well-being. This dual-action strategy could potentially improve survival rates and quality of life for patients with recurrent ovarian cancer.

What evidence suggests that this combination therapy could be effective for ovarian cancer?

Research shows that DOXIL, a type of chemotherapy, effectively treats ovarian cancer. It gained approval after studies found it could shrink tumors and aid patients whose cancer has returned. In this trial, participants will receive a combination of DOXIL and Ashwagandha. Ashwagandha, a natural herb, is thought to have cancer-fighting properties, but it has mostly been studied in labs. Early research suggests that combining Ashwagandha with DOXIL might enhance the chemotherapy's effectiveness, though limited information exists from human studies. This trial aims to potentially boost the effects of chemotherapy and improve patient outcomes by combining Ashwagandha with DOXIL. ^{1 4 6 7 8}

Who Is on the Research Team?

Whitney Goldsberry, MD

Principal Investigator

Brown Cancer Center at University of Louisville

Are You a Good Fit for This Trial?

This trial is for women over 18 with recurrent ovarian cancer, including various subtypes, who've had at least two prior chemotherapy treatments (one platinum-based) and haven't been treated with liposomal doxorubicin. They should understand the study's experimental nature, have a life expectancy over six months, and measurable disease or elevated CA 125 levels.

Inclusion Criteria

My cancer has come back, confirmed by tests or high CA 125 levels.

My cancer can be measured or seen on tests.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I am mostly bedridden due to my health condition.

I have a serious heart lining condition.

I have been treated with liposomal doxorubicin before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Feasibility and tolerability evaluation with dose escalation of Ashwagandha in combination with DOXIL

16 weeks

4 visits (in-person, every 4 weeks)

Treatment Phase II

Evaluation of overall survival and response rate with maximum tolerable dose of Ashwagandha and DOXIL

Up to 2 years

10 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Ashwagandha
• DOXIL
• Withaferin A

Trial Overview The study tests combining Ashwagandha (ASWD) in tablet form at different doses (2g, 4g, 8g) with DOXIL to find the safest high dose of ASWD. It will then assess how well this combination works to improve outcomes like complete response or stable disease in patients.

How Is the Trial Designed?

Group I: Combination of DOXIL and Ashwagandha Experimental Treatment 4 Interventions

The study contains two parts. In part 1 (Phase I), 18 patients with recurrent ovarian cancer will be recruited and administered IV with liposomal doxorubicin (DOXIL) 40 mg/m2 on day 1 of 28 days cycle for 4 cycles. Ashwagandha will be administered on daily basis for 2 years. Three doses of Ashwagandha (2 g, 4 g or 8.0 g) will be administered orally with water every day for two years to evaluate a tolerable dose of Ashwagandha. Six patients will be recruited for each dose. In part 2 Phase II), 54 additional patients with recurrent ovarian cancer will be recruited and administered with DOXIL IV (40 mg/m2) and maximum tolerable dose of Ashwagandha (determined from part 1) in the form tables orally with water on daily basis for two years. The survival rate (SR), complete response (CR) and partial response (PR) will be evaluated.

DOXIL is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Doxil for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Approved in European Union as Caelyx for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma
• Breast cancer

Approved in Canada as Liposomal Doxorubicin for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Approved in Japan as Doxorubicin Hydrochloride Liposome Injection for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma

Who Is Running the Clinical Trial?

Sham Sunder Kakar

Lead Sponsor

Trials

1

Recruited

70+

University of Louisville Health Care

Collaborator

Trials

1

Recruited

70+

Published Research Related to This Trial

Caelyx/Doxil, a pegylated liposomal formulation of doxorubicin, has a unique pharmacokinetic profile that allows it to effectively target tumor sites while reducing toxicity compared to traditional doxorubicin.

It has been approved by the FDA and EMEA for treating AIDS-related Kaposi's sarcoma and recurrent epithelial ovarian cancer, and is being investigated for use in various other cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. Tejada-Berges, T., Granai, CO., Gordinier, M., et al.[2022]

A modified regimen of liposomal doxorubicin at 40 mg/m² every 4 weeks resulted in significantly less toxicity compared to the standard dose, with only 12% of patients experiencing grade 2 hand-foot syndrome and 8% experiencing stomatitis.

Despite the reduced toxicity, the treatment showed limited antineoplastic activity, with 9% of evaluable patients demonstrating an objective response in a group of 49 patients with platinum/paclitaxel-refractory ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Markman, M., Kennedy, A., Webster, K., et al.[2022]

Doxil-liposomal topotecan (Topophore C) combinations showed promising synergistic effects in treating ovarian cancer, particularly in the ES-2 and OVCAR-3 cell lines, indicating enhanced therapeutic potential compared to individual drugs.

In animal models, the combination of Topophore C and Doxil significantly increased median survival time to 52 days, compared to 18 days for untreated animals and 40 days for Topophore C alone, demonstrating the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity. Patankar, NA., Pritchard, J., van Grinsven, M., et al.[2018]

In a study of 42 patients receiving cumulative doses of pegylated liposomal doxorubicin (doxil) exceeding 500 mg/m2, none developed clinical congestive heart failure, indicating a favorable safety profile for higher doses compared to traditional doxorubicin.

While five patients experienced a drop in left ventricular ejection fraction (LVEF), the overall risk of cardiomyopathy appears significantly lower with doxil, even in patients previously treated with doxorubicin, suggesting that doxil may be a safer option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. Safra, T., Muggia, F., Jeffers, S., et al.[2022]

The study found that the generic doxorubicin liposome injection developed by Sun Pharmaceuticals (SPIL) has a plasma and tissue distribution profile that is generally comparable to the reference product, Caelyx®, in murine models.

Minor differences in tissue distribution were noted, but these variations were likely due to biological differences rather than significant discrepancies between the two formulations, suggesting that SPIL's product may offer a similar benefit-risk profile as Caelyx®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx® (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. Burade, V., Bhowmick, S., Maiti, K., et al.[2018]

The study developed a nano-liposomal formulation that effectively co-delivers cisplatin and doxorubicin, achieving high entrapment efficiencies of 85.29% and 73.62%, respectively, which helps to overcome chemotherapy resistance in ovarian cancer.

Cisplatin and doxorubicin-loaded liposomes demonstrated enhanced cytotoxicity against ovarian cancer cells (A2780) compared to free drug combinations, while also showing improved biocompatibility with normal cells, indicating a promising strategy for reducing toxicity and improving treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation, characterization, and Co-delivery of cisplatin and doxorubicin-loaded liposomes to enhance anticancer Activities. Bahrami Parsa, M., Tafvizi, F., Chaleshi, V., et al.[2023]

Pegylated liposomal doxorubicin (Doxil) has a unique toxicity profile compared to conventional doxorubicin, showing less cardiac toxicity and minimal hair loss, while primarily causing mucocutaneous toxicities and mild myelosuppression.

Doxil is particularly effective in treating AIDS-related Kaposi's sarcoma and recurrent ovarian cancer, with ongoing research exploring its potential in other cancers and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Gabizon, AA.[2022]

In a phase II study involving 63 patients with ovarian cancer, pegylated liposomal doxorubicin (Doxil) showed a response rate of 19% in patients with measurable disease and a median overall survival of 10 months, indicating its efficacy in a heavily pretreated population.

Doxil was well tolerated, with manageable side effects; serious toxicities were relatively low, and nausea and vomiting were uncommon, suggesting a favorable safety profile compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of liposomal doxorubicin in advanced gynecologic cancers. Israel, VP., Garcia, AA., Roman, L., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05610735

Combination Therapy for Recurrent Ovarian Cancer This is a two-part open-label clinical trial of ASWD (Ashwagandha) administered to patients with recurrent ovarian cancer in combination with liposomal ...

2. withpower.com withpower.com/trial/ashwagandha-doxil-for-ovarian-cancer-03eda

Ashwagandha + DOXIL for Ovarian Cancer DOXIL, a form of the chemotherapy drug doxorubicin, has been shown to have a different safety profile compared to traditional doxorubicin, with less heart- ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29995186/

Two Multicenter Phase I Randomized Trials to Compare ... Two Multicenter Phase I Randomized Trials to Compare the Bioequivalence and Safety of a Generic Doxorubicin Hydrochloride Liposome Injection ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/050718Orig1s046.pdf

NDA 50-718/S-46 | FDA See full prescribing information for. DOXIL. DOXIL.. (doxorubicin hydrochloride liposome injection), for intraveno us use. Initial U.S. ...

5. cancernetwork.com cancernetwork.com/view/doxil-wins-full-approval-relapsed-ovarian-ca

Doxil Wins Full Approval for Relapsed Ovarian Ca FDA granted Doxil accelerated approval in 1999 for the treatment of metastatic ovarian cancer on the basis of three phase II studies that showed tumor ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2007/050718s029lbl.pdf

Doxil Label - accessdata.fda.gov The safety data described below reflect exposure to DOXIL in 1310 patients including: 239 patients with ovarian cancer, 753 patients with AIDS-related Kaposi's ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8954542/

Withania somnifera: Progress towards a Pharmaceutical ... This review substantiates WS as a potential immunomodulatory, anticancer, and chemopreventive agent and highlights its potential use in cancer treatment.

8. careacross.com careacross.com/clinical-trials/trial/NCT05610735

Combination Therapy for Recurrent Ovarian Cancer Description: DOXIL will be administered IV as 40 mg/m2 IV every four weeks for 4 cycles or until disease progression and/or unacceptable toxicity, whichever ...